Effects of Estrogen on Muscle Gain During 12-weeks of Exercise in Post-menopausal Women (HER-MUSCLE)

As females age and transition through menopause, the decline in oestrogen level profoundly affects skeletal muscle mass and function. HER-MUSCLE aims to unravel the mechanisms by which oestrogen enhances muscle growth, providing insights for targeted therapies to improve the health and physical function of postmenopausal females.

Focusing on postmenopausal females, an increasingly at-risk demographic, HER-MUSCLE addresses a critical gap in understanding how oestrogen influences muscle mass and function during anabolic (exercise) conditions.

The project involves:

1. Clinical Trial: Postmenopausal females will receive either oestrogen or placebo, twelve weeks of exercise training to detect oestrogen regulatory role on muscle mass and function.
2. Molecular Analysis: Advanced techniques will study the muscle microenvironment, focusing on muscle stem cells (MuSCs), fibro-adipogenic progenitors (FAPs), and other cells critical for muscle regeneration and maintenance.
3. Mitochondrial Function assessed in vivo via magnetic resonance spectroscopy: The impact of oestrogen on mitochondrial health will be examined, exploring how it preserves mitochondrial function and ability to recovery and resist fatigue in response to muscle contractions.

Our preliminary data indicate that oestrogen can promote muscle protein synthesis. HER-MUSCLE aims to pave the way for novel therapeutic strategies to manage sarcopenia in postmenopausal women, ultimately leading to better health outcomes and enhanced well-being for this growing population segment.

Study Overview

• Status: Recruiting
• Conditions: Exercise Training; Menopause Related Conditions
• Intervention / Treatment: Drug: Estrogel; Behavioral: Physical exercise

Detailed Description

As females age and transition through menopause, the decline in oestrogen level profoundly affects skeletal muscle mass and function. HER-MUSCLE aims to unravel the mechanisms by which oestrogen enhances muscle growth, providing insights for targeted therapies to improve the health and physical function of postmenopausal females.

Focusing on postmenopausal females, an increasingly at-risk demographic, HER-MUSCLE addresses a critical gap in understanding how oestrogen influences muscle mass and function during anabolic (exercise) conditions.

The project involves:

1. Clinical Trial: Postmenopausal females will receive either oestrogen or placebo, twelve weeks of exercise training to detect oestrogen regulatory role on muscle mass and function.
2. Molecular Analysis: Advanced techniques will study the muscle microenvironment, focusing on muscle stem cells (MuSCs), fibro-adipogenic progenitors (FAPs), and other cells critical for muscle regeneration and maintenance.
3. Mitochondrial Function assessed in vivo via magnetic resonance spectroscopy: The impact of oestrogen on mitochondrial health will be examined, exploring how it preserves mitochondrial function and ability to recovery and resist fatigue in response to muscle contractions.

Our preliminary data indicate that oestrogen can promote muscle protein synthesis. HER-MUSCLE aims to pave the way for novel therapeutic strategies to manage sarcopenia in postmenopausal women, ultimately leading to better health outcomes and enhanced well-being for this growing population segment.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mette Hansen, PhD; Phone Number: +4551666551; Email: mhan@ph.au.dk

Study Locations

• Denmark
  • Jutland
    • Aarhus, Jutland, Denmark, 8000
      • Recruiting
      • Aarhus University
      • Contact: Mette Hansen, PhD; Phone Number: +4551666551; Email: mhan@ph.au.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 1-10 years since last menstrual bleeding
• Age > 40 years old
• BMI 20-30

Exclusion Criteria:

• Follicular stimulating hormone < 30 mmol/L
• Systematic strength training during the last year (> 1 strength training session per week)
• Injuries to the legs which may prevent participation in the physical training program
• Magnetizable metals or electrical devices implanted in the body, such as a pacemaker
• Use of medication that can influence the effect of immobilization and/or training
• Muscular or joint disorders which may affect the results
• Metabolic diseases (such as diabetes and cardiovascular diseases)
• Previous or present liver or cancer disease
• Current or previous thrombosis
• Porphyria
• Epilepsia
• Systemic autoimmune disease
• Edema
• Smoking or use of other nicotine containing products
• Claustrophobia
• Addictive behavior, defined as abuse of cannabis, opioids, or other intoxicating substances.
• Lack of ability to cooperate
• Blood parameters out of normal range at the health check
• Blood pressure above 140/90 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Estrogen; Transdermal Estrogen Administration	Drug: Estrogel; The other group receive placebo treatment; Behavioral: Physical exercise; Both groups will go through 12 weeks of supervised physical exercise, consisting of both strength training and cardiovascular training
Placebo Comparator: Placebo; Transdermal placebo administration	Behavioral: Physical exercise; Both groups will go through 12 weeks of supervised physical exercise, consisting of both strength training and cardiovascular training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle mass	Magnetic resonance imaging of one leg before and after intervention	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure		12 weeks
Mitochondria Function in vivo measured as phosphocreatine recovery rate	The dominant foot will be attached to a pedal mounted on the patient bed and a dedicated 31P surface coil will be secured over the tibialis anterior muscle. The pedal is designed to allow dynamic contractions of the tibialis anterior muscle while changes in metabolites from the tibialis anterior muscle are acquired non-invasively with the 31P coil. Two protocols will be performed: Firstly, 10 repeated contractions (one per 3 sec with a load representing 30% of maximal force) will result in a depletion (30-40%) of phosphocreatine (PCr). The rate constant for PCr recovery over 10 min will be used as an index of in vivo mitochondrial function. Secondly, a total of 80 repeated contractions (one per 3 sec with a load representing 30% of maximal force) will be used to quantify muscle fatigue and concurrent changes in muscle metabolites and intracellular pH (based on the chemical shift between inorganic phosphate and PCr).	12 weeks
Mitochondria Function in vitro measured as maximal oxygen consumption	All measurements were performed in duplicate using an Oxygraph-2k (Oroboros, Austria), in hyperoxygenated chambers (250-450 nmol O₂/mL). Respiratory Control Ratio was used to evaluate mitochondrial efficiency. It was calculated as the ratio of maximal ADP-supported respiration (with complex I + II substrates) to leak respiration. Leak respiration reflects oxygen consumption in the absence of ATP synthesis, when only substrates are present and no ADP is added.	12 weeks
Body composition	DXA	12 weeks
Satelitte cells	Histochemical Analysis of Muscle tisse	12 weeks
Muscle fiber cross-sectional Area	Histochemical Analysis of Muscle Tissue	12 weeks
Expression of Muscle proteins	Western blotting analysis	12 weeks
FACS Analysis	FACS analysis to quantify and isolate Muscle satelitte celss, fibro-adipogenic progenitors and macrofages	12 weeks
Muscle Strength	Includes measure of leg strength during isometric and dynamic maximal voluntary contractions in a dynamometer (Humac Norm, CSMi, Massachusetts, United States) with a hip angle of 90°. In addition, finger strength, hand grip strength	12 weeks
Functional test	Includes counter-movement jump on a speed force-platform (Swift performance, Australia). To measure dexterity, the nine-hole peg test will be applied.	12 weeks
Cardiovascular fitness	Vo2max test on a bike and estimated via Ventriject	12 weeks
Maximal fat oxidation rate	Bike test with increasing intensity steps	12 weeks
Resisting metabolic rate		12 weeks
Questionaires	The participant will be asked to fill out recognized questionnaires about menopause (Menopause Rating Scale), sleep, diet and training readiness (modified version of "The wellbeing review"	12 weeks
Physical Activity Level	Accelerometers	12 weeks
Flexibility	sit-and-reach test	12 weeks
Knee laxity	Lachmeter test	12 weeks
Protein expression in adipose tissue	Two adipose tissue biopsies will be obtained from each participant by a trained physician before and after 12 weeks from subcutaneous abdominal and gluteal regions. Western blotting analysis of expression of proteins related to lipolysis and lipogenesis	12 weeks
Blood volume	Determination of blood volume and haemoglobin mass by the carbon-monoxide rebreathing method	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Height		12 weeks
Blood analysis	estradiol testosteron SHBG progesteron FSH LH Insulin IGF-1 + IGF-1 Bp3 - metabolit LDL - lipid HDL - lipid Triglycerid - lipid Total cholesterol Kortisol P1NP CTX1 - knogle HbA1c PTH CRP p-kreatinase p-kreatinin+eGFR p-calcium p-alanintransaminase p-albumin Alkalisk fosfatase (ALP) 6-keto-PGF1a Endothelin-1 s-VCAM-1 s-ICAM-1 Glucose Hæmoglobin Hæmatokrit	12 weeks
Dairy record registration	Before the intervention and during during rehabilization	12 weeks
Body mass		12 weeks

Collaborators and Investigators

• Sponsor: Mette Hansen
• Collaborators: Aarhus University Hospital; University of Copenhagen; Aalborg University
• Investigators: Principal Investigator: Mette Hansen, PhD, Aarhus University, Department of Public Health

Publications and helpful links

Helpful Links

• Project homepage

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: February 27, 2026
• First Submitted That Met QC Criteria: May 23, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 23, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Menopause; Physical exercise; Muscle strength; Muscle mass; Cardiovascular training; Strength training; Estrogen; Muscle hypertrophy; Mitochondria function
• Additional Relevant MeSH Terms: Behavior; Motor Activity; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Estradiol; Exercise
• Other Study ID Numbers: E30 HER-MUSCLE Intervention

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Do to GDPR rules, we do not plan to share

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No